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Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury

The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord inj...

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Autores principales: Ye, Lu-Xia, An, Ning-Chen, Huang, Peng, Li, Duo-Hui, Zheng, Zhi-Long, Ji, Hao, Li, Hao, Chen, Da-Qing, Wu, Yan-Qing, Xiao, Jian, Xu, Ke, Li, Xiao-Kun, Zhang, Hong-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067950/
https://www.ncbi.nlm.nih.gov/pubmed/33063740
http://dx.doi.org/10.4103/1673-5374.295347
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author Ye, Lu-Xia
An, Ning-Chen
Huang, Peng
Li, Duo-Hui
Zheng, Zhi-Long
Ji, Hao
Li, Hao
Chen, Da-Qing
Wu, Yan-Qing
Xiao, Jian
Xu, Ke
Li, Xiao-Kun
Zhang, Hong-Yu
author_facet Ye, Lu-Xia
An, Ning-Chen
Huang, Peng
Li, Duo-Hui
Zheng, Zhi-Long
Ji, Hao
Li, Hao
Chen, Da-Qing
Wu, Yan-Qing
Xiao, Jian
Xu, Ke
Li, Xiao-Kun
Zhang, Hong-Yu
author_sort Ye, Lu-Xia
collection PubMed
description The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 μg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 μM H(2)O(2). At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and β-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018.
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spelling pubmed-80679502021-04-27 Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury Ye, Lu-Xia An, Ning-Chen Huang, Peng Li, Duo-Hui Zheng, Zhi-Long Ji, Hao Li, Hao Chen, Da-Qing Wu, Yan-Qing Xiao, Jian Xu, Ke Li, Xiao-Kun Zhang, Hong-Yu Neural Regen Res Research Article The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 μg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 μM H(2)O(2). At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and β-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018. Wolters Kluwer - Medknow 2020-10-09 /pmc/articles/PMC8067950/ /pubmed/33063740 http://dx.doi.org/10.4103/1673-5374.295347 Text en Copyright: © 2021 Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Ye, Lu-Xia
An, Ning-Chen
Huang, Peng
Li, Duo-Hui
Zheng, Zhi-Long
Ji, Hao
Li, Hao
Chen, Da-Qing
Wu, Yan-Qing
Xiao, Jian
Xu, Ke
Li, Xiao-Kun
Zhang, Hong-Yu
Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title_full Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title_fullStr Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title_full_unstemmed Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title_short Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
title_sort exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067950/
https://www.ncbi.nlm.nih.gov/pubmed/33063740
http://dx.doi.org/10.4103/1673-5374.295347
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